Department of Medical Oncology, Princess Margaret Hospital Cancer Centre, Toronto, Ontario, Canada
Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
J Immunother Cancer. 2023 Aug;11(8). doi: 10.1136/jitc-2022-006500.
Immune-related adverse events (irAEs) are toxicities resulting from use of immune checkpoint inhibitors (ICIs). These side effects persist in some patients despite withholding therapy and using immunosuppressive and immune-modulating agents. Little is known about chronic irAEs and they are felt to be rare. We performed a systematic review to characterize non-endocrine chronic irAEs reported in the literature and describe their management. Ovid MEDLINE and Embase databases were searched for reports of adult patients with solid cancers treated with ICIs who experienced chronic (>12 weeks) non-endocrine irAEs. Patient, treatment and toxicity data were collected. Of 6843 articles identified, 229 studies including 323 patients met our inclusion criteria. The median age was 65 (IQR 56-72) and 58% were male. Most patients (75%) had metastatic disease and the primary cancer site was melanoma in 43% and non-small cell lung cancer in 31% of patients. The most common ICIs delivered were pembrolizumab (24%) and nivolumab (37%). The chronic irAEs experienced were rheumatological in 20% of patients, followed by neurological in 19%, gastrointestinal in 16% and dermatological in 14%. The irAE persisted for a median (range) of 180 (84-2370) days and 30% of patients had ongoing symptoms or treatment. More than half (52%) of patients had chronic irAEs that persisted for >6 months. The ICI was permanently discontinued in 60% of patients and 76% required oral and/or intravenous steroids. This is the first systematic review to assess and report on moderate/severe chronic non-endocrine irAEs after treatment with ICI in the literature. These toxicities persisted for months-years and the majority required discontinuation of therapy and initiation of immunosuppression. Further research is needed to better understand chronic irAEs, which hold potential substantial clinical significance considering the expanded use of ICIs and their integration into the (neo)adjuvant settings.
免疫相关不良反应（irAEs）是使用免疫检查点抑制剂（ICIs）引起的毒性。尽管停止治疗并使用免疫抑制和免疫调节药物，这些副作用仍在一些患者中持续存在。对于慢性 irAEs 知之甚少，人们认为它们很少见。我们进行了一项系统评价，以描述文献中报道的非内分泌性慢性 irAEs，并描述其管理方法。检索了 Ovid MEDLINE 和 Embase 数据库，以查找接受 ICIs 治疗的实体瘤成年患者经历慢性（>12 周）非内分泌性 irAEs 的报告。收集了患者、治疗和毒性数据。在确定的 6843 篇文章中，有 229 项研究包括 323 名患者符合纳入标准。中位年龄为 65（IQR 56-72），58%为男性。大多数患者（75%）患有转移性疾病，原发癌部位为黑色素瘤（43%）和非小细胞肺癌（31%）。最常使用的 ICIs 是 pembrolizumab（24%）和 nivolumab（37%）。20%的患者出现了风湿性慢性 irAE，其次是 19%的神经毒性，16%的胃肠道毒性和 14%的皮肤毒性。irAE 持续时间中位数（范围）为 180（84-2370）天，30%的患者有持续的症状或治疗。超过一半（52%）的患者有持续时间>6 个月的慢性 irAE。60%的患者永久停用了 ICI，76%的患者需要口服和/或静脉用类固醇。这是第一项在文献中评估和报告接受 ICI 治疗后中/重度非内分泌性慢性 irAE 的系统评价。这些毒性持续了数月至数年，大多数患者需要停止治疗并开始免疫抑制。需要进一步研究以更好地了解慢性 irAE，考虑到 ICIs 的广泛应用及其整合到（新）辅助治疗环境中，这些毒性具有潜在的重要临床意义。
